The present study is testing the hypothesis that alterations in fibrinolysis encountered in type 2 diabetes are determinants of the increased risk for atherosclerosis in this patient population. The major aims of the project are to: 1) determine if reproduction of the metabolic abnormalities of type 2 diabetes in normal volunteers lead to alterations in fibrinolysis encountered in individuals with this disease, 2) determine if correction of the metabolic abnormalities in type 2 diabetic patients is also accompanied by a decrease in alterations in fibrinolysis. So far we have completed most of the work proposed by the project funded by the American Diabetes Association. A major publication was accepted by Diabetes as a Rapid Publication in the issue of February of 1998 in which we were able to demonstrate that re-creation of the hyperglycemia, hyperlipidemia and hyperinsulinemia of type 2 diabetes in normal volunteers induces an increase in PAI-1 concentrations of blood reminiscent of those that are encountered in type 2 diabetes. A new piece of information has already emerged and a publication is being sent for consideration to Circulation. In this new publication we demonstrate that the combination of the alterations made before is necessary for the increase in PAI-1 since induction of hyperglycemia with mild hyperlipidemia and/or hyperlipidemia alone can not reproduce the increase in PAI-1 that we observed when the three abnormalities were induced simultaneously. Another publication that has emerged from this study is a review of the multiple cardiovascular risk factors that type 2 diabetes encompasses. The aim of the next few months in the life of this project is to complete the infusion protocols in type 2 diabetic patients. Preliminary data on those show that hyperlipidemia induced during a euglycemic hyperinsulinemia clamp decreases the concentrations of PAI-1 in blood.